It was previously shown that 1,N⁶-ethenoadenine (A) in DNA rearranges into a pyrimidine ring-opened derivative of 20-fold higher mutagenic potency in Escherichia coli (AB1157 lacU169) than the parental A (Basu et al., (1993) Biochemistry, 32, 12793-12801). We have found that at pH 7.0, stability of the N-glycosidic bond in dA is 20-fold lower than in dA. In alkaline conditions, but also at neutrality dA depurinates or converts into products: dA->B->C->D. Compound B is a product of water molecule addition to the C(2)-N(3) bond, which is in equilibrium with a product of N(1)-C(2) bond rupture in dA. Compound C is a deformylated derivative of ring-opened compound B, which further depurinates yielding compound D. Ethenoadenine degradation products are not recognized by human N-alkylpurine-DNA glycosylase, which repairs A. Product B is excised from oligodeoxynucleotides by E. coli formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease III (Nth). Repair by the Fpg protein is as efficient as that of 7,8-dihydro-8-oxoguanine, when the excised base is paired with dT and dC, but less favorable when paired with dG and dA. Ethenoadenine rearrangement products are formed in oligodeoxynucleotides also at neutral pH with the rate of about 2-3% per week at 37°C, so they may contribute to A mutations.